The human blood carries vital substances to cell tissues and organs of the body. Blood viscosity depends on blood composition, temperature, shear rate, vessel diameter, cell aggregation level, shape, deformation and plasma viscosity. Whole blood is a non-homogenous complex fluid, which exhibits very complex properties (R. G. Owens, J. Non-Newtonian Fluid Mech. 140, 57, 2006; M. Moyers-Gonzalez, R. G. Owens, and J. Fang, J. Fluid Mech. 617, 327, 2008). The circulatory system is a complex system of branching compliant tubes, which adjusts itself according to a number of control mechanisms. Because of this complexity, there is a number of variables which effect the functions, properties and responses of the circulatory system.
Early dynamic rheological measurements demonstrated a non-Newtonian behaviour of human blood (G. B. Thurston, Proceedings of the Sixth Conference of the European Society for Microcirculation, Aalborg (Karger, Basel, pp. 12-15, 1971; G. B. Thurston, Biophys. J. 12, 1205, 1972; A. Lessner et al., Theoretical and Clinical Hemorheology, Springer-Verlag, Berlin, pp. 194-205, 1971), whereas plasma can be considered as a Newtonian fluid (R. G. Owens, J. Non-Newtonian Fluid Mech. 140, 57, 2006; M. Moyers-Gonzalez, R. G. Owens, and J. Fang, J. Fluid Mech. 617, 327, 2008; M. Moyers-Gonzalez, R. G. Owens, and J. Fang, J. Non-Newtonian Fluid Mech. 155, 161, 2008; M. Moyers-Gonzalez, R. G. Owens, J. Non-Newtonian Fluid Mech. 155, 146, 2008). Non-Newtonian properties include viscoelasticity, thixotropy and shear-thinning behaviour. At low shear rates, red blood cells may form aggregates structures, causing an increased blood viscosity (G. B. Thorston and N. M. Henderson, Handbook of Hemorheology and Hemodynamcis, IOS, Amsterdam, pp. 72-90, 2007). In small vessels typical of the microcirculation system, e.g. arterioles and capillaries, where the characteristic times of the flow and the fluid become comparable, blood presents a viscoelastic behaviour (R. G. Owens, J. Non-Newtonian Fluid Mech. 140, 57, 2006).
A comprehensive characterization of blood rheology and its flow dynamics is indeed very important in order to predict cardiovascular diseases, to plan vascular surgeries, to understand the transport of drugs through the circulatory system, and for the development of cardiovascular equipment as, for example, blood pumps, heart valves and stants (F. Yilmaz and M. Y. Gundogdu. Korea-Aust. Rheol. J. 20, 197, 2008). However, the manipulation of whole blood is not a straightforward task and may not always be practical primarily due to safety reasons.
Blood analog solutions are widely used for in-vitro experiments as they exhibit several advantageous characteristics such as non-toxicity, low cost and transparency (G. B. Thorston, Advances in Hemodynamics and Hemorheology, JAI Press., Inc., Connecticut, Vol. I, pp. 1-30, 1996). A number of these fluids present rheological characteristics similar to human blood and are typically based on polymer solutions. One of the known solutions contains polystyrene spheres in a mixture of water, dextran 70 and calcium chloride to stimulate the aggregation process (E. Fukada, G. V. F. Seaman, D. Liepsch, M. Lee, and L. Friis-Baastad, Biorheology 26, 401, 1989). In addition, aqueous solutions of a polyacrylamide (PAA) and xanthan gum (XG) have been developed, in which the addition of glycerine was used to tune the blood rheology at different haematocrit levels (K. K. Brookshier and J. M. Tarbell, Biorheology 30, 107, 1993). It was found, however, that at high shear rates, the known blood analogs tend to exhibit higher viscosity and elasticity than whole blood (G. Vlastos, D. Lerche, B. Koch, O. Samba, and M. Pohl, Rheol. Acta 36, 160, 1997).
Since blood rheology is extremely complex, it is difficult to develop analog fluids that yield a complete description of all the rheological properties of blood. Typically, these fluids are chosen based on the density and shear viscosity. The known blood analog solutions described above suffer from the problem that the viscosity is essentially independent from the shear rate of the solution. Real blood exhibits a shear rate diminishing effect when viscosity increases.
The flow of blood analog solutions can be investigated in microchannels with dimensions comparable to small human vessels and flow visualisation techniques (P. C. Sousa et al., Extensional flow of blood analog solutions in microfluidic devices, Biomicrofluidics 5, 014108, 2011). The use of microchannels is advantageous because they are simplified representations of intensity stenoses typical of diseased microcirculatory vessels. Therefore, also possible medical conditions such as haemorrhage or shock can be addressed using blood substitute solutions. The rheology of blood analog fluids can be analysed by rotational rheometers or capillary brake-up extensional rheometers to determine the relaxation time of the fluid in extensional flow.
The studies known so far demonstrate that, at low flow rates, the known blood analog polymer solutions exhibit Newtonian-like flow patterns, i.e. an increase of the flow rate results in an appearance of symmetric vortices upstream of the contraction that increases in size with the flow rate due to the enhancement of elastic effects. When the flow rate is further increased, inertial effects also become important and symmetric vortices are observed downstream of the abrupt expansion similar to the Newtonian fluid flow.
There are also alternative solutions such as compositions comprising human serum albumin and amino acid solutions for use in treatment of hypovolemia or shock (U.S. Pat. No. 7,696,176 B1). A similar intravenous blood-replacement solution for rapidly restoring normal blood viscosity, rheology, osmolarity and hemodynamic stability has been described in U.S. 2007/0207962 A1. The solution comprises fibrinogen, albumin, fibronectin and an electrolyte.